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ALBumin Italian Outcome Septic Shock-BALANCED Trial (ALBIOSS-BALANCED) (ALBIOSS-BAL)

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ClinicalTrials.gov Identifier: NCT03654001
Recruitment Status : Recruiting
First Posted : August 31, 2018
Last Update Posted : December 1, 2020
Sponsor:
Collaborator:
Istituto Di Ricerche Farmacologiche Mario Negri
Information provided by (Responsible Party):
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Brief Summary:

Septic shock is a devastating condition often observed in ICU. It is characterized by pro-inflammatory and immune responses, organ failures, high incidence of AKI and lethality. Fluid resuscitation is pivotal as supportive therapy. At present, there are no effective therapies to improve survival of such clinical condition, often characterized by a mortality as high as 40% during the first 90 days from diagnosis.

This project proposes a large 2-by-2 factorial randomized clinical trial testing the efficacy of albumin and the low- chloride balanced crystalloid solutions (either Ringer Lactate, Ringer Acetate, or Crystalsol - BAL) in septic shock.

The investigators have recently concluded a multicenter, randomized trial, the ALBIOS trial, in which, in a post-hoc analysis, albumin, in addition to crystalloids, reduced 90-day mortality in patients with septic shock, as compared to crystalloids alone (Caironi P et al, 2014). Crystalloids with supra-physiological chloride content may deteriorate renal perfusion, increasing the risk of acute kidney injury (AKI) and mortality.


Condition or disease Intervention/treatment Phase
Septic Shock Biological: Albumin Other: Balanced Phase 3

Detailed Description:

The project will consist of a 2-by-2 factorial, investigator-initiated, open-label, multicenter, randomized, controlled trial, with PROBE design (Prospective Randomized Open Trial with Blinded Evaluation of Outcomes), in patients with septic shock, as defined according to clinical criteria.

Patients will be randomized in a 1:1:1:1 ratio to one of the 4 study groups (Albumin + BAL, Albumin + NS, BAL, NS).

Both the primary endpoints will include events evaluated objectively: 90-day mortality and incidence of AKI, as assessed by KDIGO criteria (KDIGO Acute Kidney Injury Work Group, 2012).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1252 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description: 2-by-2 factorial design, open-label, multicenter, randomized, controlled trial, in patients with septic shock, as defined according to clinical criteria. Patients will be randomized in a 1:1:1:1 ratio to one of the 4 groups (Albumin + BAL, Albumin + NS, BAL, NS).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Albumin Replacement and Balanced Solution in Patients With Septic Shock (the ALBIOSS-BALANCED Trial): a 2-by-2 Factorial, Investigator-initiated, Open- Label, Multicenter, Randomized, Controlled Trial
Actual Study Start Date : May 7, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : February 28, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock

Arm Intervention/treatment
Experimental: Albumin + Balanced

Human Albumin In parallel with fluid administration for volume resuscitation, patients will receive 400 ml of 20% albumin solution both at randomization (D0) and at day 1 (D1). Subsequently, from day 2 (D2) until day 90 (D90) or ICU discharge (whichever comes first), 20% albumin will be administered on a daily basis, to maintain serum albumin concentration equal to or greater than 30 g/L, based upon serum albumin determination.

Balanced crystalloid solutions

According to the preference and the standard use of the participating center:

  • Ringer Lactate
  • Ringer Acetate
  • Crystalsol
Biological: Albumin
Human Albumin In parallel with fluid administration for volume resuscitation, patients will receive 400 ml of 20% albumin solution both at randomization (D0) and at day 1 (D1). Subsequently, from day 2 (D2) until day 90 (D90) or ICU discharge (whichever comes first), 20% albumin will be administered on a daily basis, to maintain serum albumin concentration equal to or greater than 30 g/L, based upon serum albumin determination.

Other: Balanced
Balanced crystalloid solutions are traditionally crystalloid solutions containing a relatively low concentration of chloride as compared to 0.9% NaCl containing solutions (Normal Saline).
Other Name: Ringer Lactate, Ringer Acetate, Crystalsol

Experimental: Albumin + Saline

Human Albumin In parallel with fluid administration for volume resuscitation, patients will receive 400 ml of 20% albumin solution both at randomization (D0) and at day 1 (D1). Subsequently, from day 2 (D2) until day 90 (D90) or ICU discharge (whichever comes first), 20% albumin will be administered on a daily basis, to maintain serum albumin concentration equal to or greater than 30 g/L, based upon serum albumin determination.

Normal Saline Na+ 154 mEq/L, Cl- 154 mEq/L (0.9% NaCl).

Biological: Albumin
Human Albumin In parallel with fluid administration for volume resuscitation, patients will receive 400 ml of 20% albumin solution both at randomization (D0) and at day 1 (D1). Subsequently, from day 2 (D2) until day 90 (D90) or ICU discharge (whichever comes first), 20% albumin will be administered on a daily basis, to maintain serum albumin concentration equal to or greater than 30 g/L, based upon serum albumin determination.

Experimental: Balanced
Balanced crystalloid solutions (Ringer Lactate, Ringer Acetate, Crystalsol)
Other: Balanced
Balanced crystalloid solutions are traditionally crystalloid solutions containing a relatively low concentration of chloride as compared to 0.9% NaCl containing solutions (Normal Saline).
Other Name: Ringer Lactate, Ringer Acetate, Crystalsol

No Intervention: Saline
Normal Saline Na+ 154 mEq/L, Cl- 154 mEq/L (0.9% NaCl).



Primary Outcome Measures :
  1. All-cause 90-day mortality [ Time Frame: Up to 90 days ]
    All-cause death from randomization to 90 days

  2. Combined co-primary endpoint [ Time Frame: Up to 90 days ]
    The composite of all-cause death from randomization to 90 days and new occurrence of acute kidney injury (AKI).


Secondary Outcome Measures :
  1. ICU mortality [ Time Frame: Up to ICU discharge, a median of 9 days ]
    All-cause death occurring in Intensive Care Unit (ICU)

  2. In-hospital mortality [ Time Frame: Up to hospital discharge, a median of 20 days ]
    All-cause death occurring during hospital stay

  3. 1-year mortality [ Time Frame: Up to 1 year ]
    All-cause death from randomization to 1 year

  4. SOFA score [ Time Frame: Up to 90 days or ICU discharge - a median of 9 days - whichever comes first ]
    Severity and incidence of organ failures, as assessed by the Sequential Organ Failure Assessment (SOFA) score. SOFA score is used to determine the extent of organ function in a patient while in the intensive care unit. The score is based on 6 different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. The scale of each score ranges from 0 (no dysfunction) to 4 (maximal dysfunction). The 6 scores are then added up to provide a global score: the highest the value, the worst the condition of the patient.

  5. Incidence of AKI [ Time Frame: Up to 90 days or ICU discharge - a median of 9 days - whichever comes first ]
    Assessed by the Kidney Disease Improving Global Outcome (KDIGO) criteria as any of the following: (1) increase in serum creatinine >=0.3 mg/dl (26.5 mmol/l) within 48 hours; or (2) increase in SCr to >=1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or (3) urine volume <0.5 ml/kg/h for 6 hours.

  6. RRT [ Time Frame: Up to 90 days or ICU discharge - a median of 9 days - whichever comes first ]
    First use of Renal Replacement Therapy (RRT) during ICU stay

  7. Need for vasopressors [ Time Frame: Up to 90 days or ICU discharge - a median of 9 days - whichever comes first ]
    Duration of the need for vasopressors during ICU stay

  8. Mechanical ventilation [ Time Frame: Up to 90 days or ICU discharge - a median of 9 days - whichever comes first ]
    Duration of mechanical ventilation during ICU stay

  9. Secondary infections in ICU [ Time Frame: Up to 90 days or ICU discharge - a median of 9 days - whichever comes first ]
    Incidence of secondary-acquired infections during ICU stay

  10. Duration of stay in ICU [ Time Frame: Up to ICU discharge, a median of 9 days ]
    Duration expressed as number of days spent in ICU

  11. Duration of stay in hospital [ Time Frame: Up to hospital discharge, a median of 20 days ]
    Duration expressed as number of days spent in hospital


Other Outcome Measures:
  1. Severe metabolic acidosis [ Time Frame: Up to 90 days or ICU discharge - a median of 9 days - whichever comes first ]
    Incidence of severe metabolic acidosis

  2. Severe hyperkalemia [ Time Frame: Up to 90 days or ICU discharge - a median of 9 days - whichever comes first ]
    Incidence of severe hyperkalemia



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients with septic shock if they meet the two following criteria:

  1. Presence of an infection (known or suspected) in at least one site:

    1. Lung
    2. Abdomen
    3. Urinary tract
    4. Others (blood, skin and soft tissues, central nervous system, bones and joints, cardiac system, reproductive organs).
  2. Presence of a severe and acute, sepsis-related cardiovascular failure (as assessed by the SOFA score - see Annex 1), requiring vasopressor to maintain mean arterial pressure >=65 mmHg, despite adequate volume resuscitation a) Cardiovascular SOFA score > 2 (3 or 4) If the patient is unable to provide informed consent, she/he can be included in the trial provided that the requirements of ongoing laws are fulfilled; details on this approach are provided in the protocol, par 11.1 and related Annex 3. The patient will be informed about having been included in a clinical trial, as soon as she/he will regain consciousness.

Exclusion Criteria:

  1. Age < 18 years
  2. Moribund state
  3. Known or suspected adverse reaction to albumin administration
  4. Septic shock in patients with traumatic brain injury or a clinically active cerebral lesion (known or suspected)
  5. Severe congestive heart failure (NYHA III and IV classes)
  6. Clinical situations in which the use of albumin is known or supposed to be clinically beneficial (hepatic cirrhosis with ascites, malabsorption syndrome or protein-losing enteropathy, nephrotic syndrome, burns)
  7. More than 24 hours after the onset of septic shock
  8. Religious objection to the administration of human blood products
  9. Presence of chronic end-stage renal disease
  10. Severe hyperkalemia
  11. Enrollment in other experimental interventional studies

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03654001


Contacts
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Contact: Antonio Pesenti, MD +390255033231 antonio.pesenti@unimi.it
Contact: Pietro Caironi, MD +393316171966 pietro.caironi@unito.it

Locations
Show Show 48 study locations
Sponsors and Collaborators
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Istituto Di Ricerche Farmacologiche Mario Negri
Investigators
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Principal Investigator: Pietro Caironi, MD AOU S. Luigi Gonzaga, Orbassano
Publications of Results:
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Responsible Party: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
ClinicalTrials.gov Identifier: NCT03654001    
Other Study ID Numbers: RF-2016-02361583
First Posted: August 31, 2018    Key Record Dates
Last Update Posted: December 1, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico:
Septic Shock
Albumin
Balanced crystalloids
Additional relevant MeSH terms:
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Shock, Septic
Shock
Pathologic Processes
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation